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Article | Open Access

Modulation of Bax and Bcl-2 genes by secondary metabolites produced by Penicillium rubens JGIPR9 causes the apoptosis of cancer cell lines

Prerana Venkatachalam,, Varalakshmi Kilingar Nadumane ( )
Department of Biotechnology, School of Sciences, JAIN (Deemed-to-be University), Bengaluru, India
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Abstract

Search for an efficient anti-cancer compound of natural origin with well-defined mechanisms of action is an important scientific pursuit today, due to cancer being the second leading cause for the death of affected people. The members of the genus Penicillium are one of the important sources of bioactive compounds. In the present study, Penicillium rubens, isolated from a garden soil in Madurai district of Tamil Nadu, was found to produce a highly promising anti-cancer metabolite. The percentage viabilities of HepG2, HeLa and MCF-7 cancer cells treated with the bioactive fraction (P5) isolated from P. rubens, ranged between 40-50% after 96 h. Apoptosis induction was found to be the major reason for the observed reduction in cancer cell proliferation and cell count which was confirmed by caspase activity, DNA fragmentation, clonogenic assay, cell cycle analysis and LDH assays. The upregulation of proapoptotic Bax, coupled with the downregulation of anti-apoptotic Bcl-2 expressions were confirmed by RT-qPCR and flow cytometry methods. The current study also indicated an upregulation of p53 which further strengthened the apoptogenic property of P5 fraction. Non-toxicity of P5 was demonstrated on normal peripheral lymphocytes. The analysis of P5 fraction through GC-MS indicated the presence of indole-2, 3-(4,4-dimethyl-3-thiosemicarbazone) as one of the major compounds.

Keywords

Cytotoxicitycell cyclesecondary metabolitescaspase activitiesBax expressionPenicillium rubens

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Mycology
Volume 12 Issue 2,
June 2021
Pages 69-81
DOI: 10.1080/21501203.2019.1707315
Cite this article:
Venkatachalam P, Nadumane VK. Modulation of Bax and Bcl-2 genes by secondary metabolites produced by Penicillium rubens JGIPR9 causes the apoptosis of cancer cell lines. Mycology, 2021, 12(2): 69-81. https://doi.org/10.1080/21501203.2019.1707315

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Received: 29 September 2019
Accepted: 03 December 2019
Published: 26 December 2019
© 2019 The Author(s).

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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